Figure 2. Egyptian Ebers papyrus (circa 16th century BCE)
The common cold as its name implies is very common; it is the most common human disease known to man, as every person is susceptible to it, and it affects people globally. Annual records indicate that adults are usually sick with the cold two to five days a year while children are sick with the cold six to twelve days a year, thereby becoming the leading cause of lost workdays, schooldays, and doctor visits. [4] According to the Centers for Diseases Control and Prevention (CDC), 22 million school days are lost annually in the United States due to the common cold. [4] While no one particular group is especially targeted by the common cold viruses, certain groups of people living in developing countries and the elderly are more prone to contract the disease due to lac k of personal hygiene and a weakened immune system respectively. Besides being common, it is also one of the oldest known diseases. Although its cause was only recognized in the 1950’s, the disease has affected people since the 16th century BCE, when Egyptian doctors described its symptoms and their treatments in the Egyptian Ebers papyrus, known today as the oldest existing medical text.
Figure 3. Does Being Cold Make You Sick?
Etymology also indicates that the disease was give then name “cold” in the 1530s because of the similarities between the symptoms of the disease and of the symptoms of those exposed to cold weather. [11] This lead to the traditional belief that a person is more susceptible to a cold in cold weather. While there has been no scientific correlation found to prove this belief, it is widely believed that cold weather can lead to a weakened immune system, which greatly increases the chance of falling sick with a cold. At the same time, poor personal hygiene and increased contact with an infected individual increases the probability of transferring the viruses in the environment from the hand to the nose or eyes, where infection occurs.
Figure 4. Image of human rhinovirus 16.
Over 200 viruses can cause the common cold, the rhinovirus being the most likely culprit 30-50% of the time. [4] Once infected, there is an estimated incubation period of about 2-3 days but symptoms can be observed within 16 hours of infection. The infected person begins to display basic symptoms such as sneezing, a runny nose, and a scratchy throat, which can last for one to two. These symptoms by themselves are mild and a person can easily recover. However, without proper rest, proper care, and sufficient hydration, it can lead to lingering symptoms such as a post-viral cough, sinus infections, ear infections, or even result in pneumonia. Since the common cold is such a widespread disease and no cure is available, it is imperative that people reduce their likelihood of contracting the disease by engaging in proper personal hygiene such as frequent hand washing, maintain a strong immune system, and wear masks around infected individuals to prevent possible contraction. In order to prevent the spread of germs and the common cold viruses within confined classrooms, schools have taken measures to educate their students about personal hygiene.
Due to the nature of the disease, medications taken for a cold do not shorten the length of the infection but merely provide symptomatic relief. Antibiotics also do not cure the infected person of the disease because it is a viral based disease, not bacterial based. As a result, taking antibiotics to cure the common cold can lead to the body’s strengthened resistance to these antibiotics. Many people usually self-medicate with medications such as ibuprofen, antihistamines, analgesics, humidified air, and/or cough syrup to relieve their runny nose andsore throat. [3] Medication used to treat influenza, such as Amantadine or better known as Symmetrel, can potentially be used to treat people with the common cold.
Figure 5. Amantadine's 2D structural formula.
Figure 6. Amantadine's 3D conformer.
Figure 7. Amantadine as 3D ball-and-stick model.
Figure 8. Amantadine as capsules.
In October 1966, the synthetic drug Amantadine was approved by the U.S. Food and Drug Administration (FDA) as medication against the Asian influenza and later on for the treatment of Influenzavirus A. In 1969, Amantadine was accidentally discovered to have an effect on Parkinson’s Disease, helping to reduce its symptoms in patients. However, the drugs full effect on Parkinson’s patients has yet to be determined. Amantadine has the chemical formula C10H17N, a molecular weight of 151.24868 g/mol, and the CAS number 768-94-5. [2] Adamantine is ingested in a capsule and the most common side effects caused by ingestion of Adamantine include nausea, dizziness, and insomnia. Additionally, Adamantine is more commonly known as Symmetrel, and has various chemical names such as 1-Aminoadamantane, Adamantylamine, Symadine, and many more. Numerous companies and laboratories, such as Aidarex Pharmaceuticals Llc., Upsher-Smith Laboratories Inc., and Endo Pharmaceuticals Inc., manufacture Amantadine, with Endo Pharmaceuticals coining the trade name Symmetrel. Furthermore, it is a patented drug and has undergone clinical trials alongside other antiviral drugs such as Ribavirin and Oseltamivir. [7] These trials proved that Amantadine is effective in treating prophylactic diseases such as influenza. [5] However, due to increased resistance, Amantadine is no longer used for treatment of influenza. Rimantadine is a derivative of Amantadine and they both have very similar structures and biological properties. As a result, both Rimantadine and Amantadine are no longer used to treat influenza. Currently, Ribavirin, Oseltamivir, Zanamivir are used instead. Amantadine has 2 mechanisms of antiviral action. Firstly, it is able to interfere with the function of the transmembrane domain of the viral M2 protein by sterically blocking the M2 channel, thereby preventing the release of viral nucleic acid into the host cell, effectively ceasing infection of the host cell. Secondly, it can also prevent virus assembly during viral replication, thereby hindering the formation of more viruses. [1]
Figure 9. Structure of Influenza virus.
The M2 protein is made up of 97 amino acids and is a transmembrane channel found on the viral envelope of the Influenza A virus. [9] It is only active in low pH, indicating that the environment influences the function of the protein. The M2 protein plays a role in the early and late stages of the replication cycle of the influenza virus, aiding in budding of the virus to the host cell. Therefore, drugs affecting the function of the M2 protein are likely to result in a cessation of the infection as the virus can no longer replicate and infect other healthy cells. Being a channel, its main function is to maintain its interior pH environment, especially during cell entry. In some cases, the M2 proteinhelps form filamentous strains of influenza. [8]
Even though the common cold has plagued man for centuries without a viable cure, the possibility of discovering a cure has been steadily increasing over the last decade due to advancements in scientific fields such as genetics and virology. In 2009, researchers decoded the genomes of 99 strains of common cold virus and cataloged their vulnerabilities, and essentially became one step closer to finding a cure. [12] Researchers claimed that with this new knowledge, drugs could potentially be produced to effectively cure the common cold, instead of merely treating its symptoms. In 2010, scientists at a Cambridge laboratory discovered that the body’s immune system has its own natural virus-killing capabilities even after the virus has attacked the cell. [6] This discovery opened more doors to the development of new classes of antiviral drugs that work to enhance these capabilities, possibly replacing drugs that targeted viruses. Four years into the future, a cure for the common cold has yet to be discovered. [10]
The Common Cold
The common cold as its name implies is very common; it is the most common human disease known to man, as every person is susceptible to it, and it affects people globally. Annual records indicate that adults are usually sick with the cold two to five days a year while children are sick with the cold six to twelve days a year, thereby becoming the leading cause of lost workdays, schooldays, and doctor visits. [4] According to the Centers for Diseases Control and Prevention (CDC), 22 million school days are lost annually in the United States due to the common cold. [4] While no one particular group is especially targeted by the common cold viruses, certain groups of people living in developing countries and the elderly are more prone to contract the disease due to lac
k of personal hygiene and a weakened immune system respectively. Besides being common, it is also one of the oldest known diseases. Although its cause was only recognized in the 1950’s, the disease has affected people since the 16th century BCE, when Egyptian doctors described its symptoms and their treatments in the Egyptian Ebers papyrus, known today as the oldest existing medical text.
Over 200 viruses can cause the common cold, the rhinovirus being the most likely culprit 30-50% of the time. [4] Once infected, there is an estimated incubation period of about 2-3 days but symptoms can be observed within 16 hours of infection. The infected person begins to display basic symptoms such as sneezing, a runny nose, and a scratchy throat, which can last for one to two. These symptoms by themselves are mild and a person can easily recover. However, without proper rest, proper care, and sufficient hydration, it can lead to lingering symptoms such as a post-viral cough, sinus infections, ear infections, or even result in pneumonia. Since the common cold is such a widespread disease and no cure is available, it is imperative that people reduce their likelihood of contracting the disease by engaging in proper personal hygiene such as frequent hand washing, maintain a strong immune system, and wear masks around infected individuals to prevent possible contraction. In order to prevent the spread of germs and the common cold viruses within confined classrooms, schools have taken measures to educate their students about personal hygiene.
Due to the nature of the disease, medications taken for a cold do not shorten the length of the infection but merely provide symptomatic relief. Antibiotics also do not cure the infected person of the disease because it is a viral based disease, not bacterial based. As a result, taking antibiotics to cure the common cold can lead to the body’s strengthened resistance to these antibiotics. Many people usually self-medicate with medications such as ibuprofen, antihistamines, analgesics, humidified air, and/or cough syrup to relieve their runny nose andsore throat. [3] Medication used to treat influenza, such as Amantadine or better known as Symmetrel, can potentially be used to treat people with the common cold.
In October 1966, the synthetic drug Amantadine was approved by the U.S. Food and Drug Administration (FDA) as medication against the Asian influenza and later on for the treatment of Influenzavirus A. In 1969, Amantadine was accidentally discovered to have an effect on Parkinson’s Disease, helping to reduce its symptoms in patients. However, the drugs full effect on Parkinson’s patients has yet to be determined. Amantadine has the chemical formula C10H17N, a molecular weight of 151.24868 g/mol, and the CAS number 768-94-5. [2] Adamantine is ingested in a capsule and the most common side effects caused by ingestion of Adamantine include nausea, dizziness, and insomnia. Additionally, Adamantine is more commonly known as Symmetrel, and has various chemical names such as 1-Aminoadamantane, Adamantylamine, Symadine, and many more. Numerous companies and laboratories, such as Aidarex Pharmaceuticals Llc., Upsher-Smith Laboratories Inc., and Endo Pharmaceuticals Inc., manufacture Amantadine, with Endo Pharmaceuticals coining the trade name Symmetrel.
Furthermore, it is a patented drug and has undergone clinical trials alongside other antiviral drugs such as Ribavirin and Oseltamivir. [7] These trials proved that Amantadine is effective in treating prophylactic diseases such as influenza. [5] However, due to increased resistance, Amantadine is no longer used for treatment of influenza. Rimantadine is a derivative of Amantadine and they both have very similar structures and biological properties. As a result, both Rimantadine and Amantadine are no longer used to treat influenza. Currently, Ribavirin, Oseltamivir, Zanamivir are used instead.
Amantadine has 2 mechanisms of antiviral action. Firstly, it is able to interfere with the function of the transmembrane domain of the viral M2 protein by sterically blocking the M2 channel, thereby preventing the release of viral nucleic acid into the host cell, effectively ceasing infection of the host cell. Secondly, it can also prevent virus assembly during viral replication, thereby hindering the formation of more viruses. [1]
The M2 protein is made up of 97 amino acids and is a transmembrane channel found on the viral envelope of the Influenza A virus. [9] It is only active in low pH, indicating that the environment influences the function of the protein. The M2 protein plays a role in the early and late stages of the replication cycle of the influenza virus, aiding in budding of the virus to the host cell. Therefore, drugs affecting the function of the M2 protein are likely to result in a cessation of the infection as the virus can no longer replicate and infect other healthy cells. Being a channel, its main function is to maintain its interior pH environment, especially during cell entry. In some cases, the M2 proteinhelps form filamentous strains of influenza. [8]
Even though the common cold has plagued man for centuries without a viable cure, the possibility of discovering a cure has been steadily increasing over the last decade due to advancements in scientific fields such as genetics and virology. In 2009, researchers decoded the genomes of 99 strains of common cold virus and cataloged their vulnerabilities, and essentially became one step closer to finding a cure. [12] Researchers claimed that with this new knowledge, drugs could potentially be produced to effectively cure the common cold, instead of merely treating its symptoms. In 2010, scientists at a Cambridge laboratory discovered that the body’s immune system has its own natural virus-killing capabilities even after the virus has attacked the cell. [6] This discovery opened more doors to the development of new classes of antiviral drugs that work to enhance these capabilities, possibly replacing drugs that targeted viruses. Four years into the future, a cure for the common cold has yet to be discovered. [10]
Bibliography
1. Amantadine HCl tablet. Upsher-Smith Laboratories, Inc. http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=5790 (accessed Feb 03, 2014)
2. Amantadine. NCBI. http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=81065610&viewopt=Deposited (accessed Feb 03, 2014)
3. Blandino, D.A. and Simasek, M. Treatment of the common cold. American Family Physician. http://www.aafp.org/afp/2007/0215/p515.html (accessed Feb 02, 2014)
4. Common cold. National Insitutute of Allergy and Infectious Diseases. http://www.niaid.nih.gov/topics/commoncold/Pages/treatment.aspx (accessed Feb 02, 2014)
5. Comparing the efficacy, safety, and tolerability of combination antivirals (amantadine, ribavirin, oseltamivir) versus oseltamivir for the treatment of influenza in adults at risk for complications (IRC003). National Institute of Allergy and Infectious Diseases (NIAID). http://www.clinicaltrials.gov/ct2/show/NCT01227967?term=amantadine+and+influenza&rank=1 (accessed Feb 04, 2014)
6. Connor, S. A cure for the common cold may finally be achieved as a result of a remarkable discovery in a Cambridge laboratory. The Independent. http://www.independent.co.uk/news/science/a-cure-for-the-common-cold-may-finally-be-achieved-as-a-result-of-a-remarkable-discovery-in-a-cambridge-laboratory-2122607.html (accessed Feb 02, 2014)
7. Drug, bio-affecting and body treating compositions. United States Patent and Trademark Office. http://www.uspto.gov/web/patents/classification/uspc514/defs514.htm (accessed Feb 04, 2014)
8. Holsinger, L.J.; Nichani, D.; Pinto, L.H.; Lamb, R.A., Influenza A virus M2 ion channel protein: a structure-function analysis. Journal of Virology 1994, 68, (3), 1551-1563.
9. M2 protein [Influenza A virus (A/crested eagle/Belgium/01/2004(H5N1))]. NCBI. http://www.ncbi.nlm.nih.gov/protein/ABB54697.1 (accessed Feb 04, 2014)
10. Hattotuwa, K, No cure for the common cold. Thorax 2003, 58, (3),230.
11. Online Etymology Dictionary. http://www.etymonline.com/index.php?term=cold (accessed Feb 02, 2014)
12. Wade, N. Cure for the common cold? Not yet, but possible. The New York Times. http://www.nytimes.com/2009/02/13/health/13iht-13cold.20160884.html?_r=0 (accessed Feb 02, 2014)